Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation.
Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation.
复制标题
对心脏负荷急剧增加的代谢反应：对丙二酰辅酶A、机械效率和脂肪酸氧化的影响。
DOI：
10.1152/ajpheart.00557.2007
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Stanley,WilliamC
中科院分区：
文献类型：
--
作者：
Zhou,Lufang;Huang,Hazel;Yuan,CelvieL;Keung,Wendy;Lopaschuk,GaryD;Stanley,WilliamC
抑制心肌脂肪酸氧化可以通过在一定的心肌能量消耗速率下增加左心室功率来提高左心室机械效率。这种现象在非缺血心肌的高负荷下尚未得到评估；因此，我们在活体猪心中施加高负荷5min，并评估用肉碱棕榈酰转移酶-I抑制剂奥非尼辛阻断线粒体脂肪酸氧化是否会提高左室机械效率。此外，测定心脏丙二酰辅酶A(肉碱棕榈酰转移酶-I的内源性抑制物)含量和乙酰辅酶A羧基酶(合成丙二酰辅酶A)的活性。采用主动脉缩窄和多巴酚丁胺输注引起的负荷增加，根据左心室压力-容量环和左心室能量消耗计算左心室效率。在未经处理的猪中，左心室功率的增加导致脂肪酸氧化和心肌丙二酰辅酶A含量增加2.5倍，但不影响乙酰辅酶A羧基酶的激活状态。随着心脏负荷的增加，乙酰辅酶A羧化酶抑制激酶AMP激活的蛋白激酶的激活状态降低了40%。奥非尼辛可抑制75%的脂肪酸氧化，对心脏能量消耗无影响，但显著增加大负荷下的左心室功率和左心室效率(37±5%比26±5%，P<；0.05)。综上所述，1)尽管丙二酰辅酶A浓度增加，但心肌脂肪酸氧化作用随着心脏负荷的短期增加而增加，2)抑制脂肪酸氧化可通过增加左心室功率而改善左心室机械效率，而不影响心脏能量消耗。
Inhibition of myocardial fatty acid oxidation can improve left ventricular (LV) mechanical efficiency by increasing LV power for a given rate of myocardial energy expenditure. This phenomenon has not been assessed at high workloads in nonischemic myocardium; therefore, we subjected in vivo pig hearts to a high workload for 5 min and assessed whether blocking mitochondrial fatty acid oxidation with the carnitine palmitoyltransferase-I inhibitor oxfenicine would improve LV mechanical efficiency. In addition, the cardiac content of malonyl-CoA (an endogenous inhibitor of carnitine palmitoyltransferase-I) and activity of acetyl-CoA carboxylase (which synthesizes malonyl-CoA) were assessed. Increased workload was induced by aortic constriction and dobutamine infusion, and LV efficiency was calculated from the LV pressure-volume loop and LV energy expenditure. In untreated pigs, the increase in LV power resulted in a 2.5-fold increase in fatty acid oxidation and cardiac malonyl-CoA content but did not affect the activation state of acetyl-CoA carboxylase. The activation state of the acetyl-CoA carboxylase inhibitory kinase AMP-activated protein kinase decreased by 40% with increased cardiac workload. Pretreatment with oxfenicine inhibited fatty acid oxidation by 75% and had no effect on cardiac energy expenditure but significantly increased LV power and LV efficiency (37 ± 5% vs. 26 ± 5%,P< 0.05) at high workload. In conclusion,1) myocardial fatty acid oxidation increases with a short-term increase in cardiac workload, despite an increase in malonyl-CoA concentration, and2) inhibition of fatty acid oxidation improves LV mechanical efficiency by increasing LV power without affecting cardiac energy expenditure.